rs77316697

Variant names:

• chr10-60278789-G-A
• rs77316697
• NM_020987.5:c.399C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-60278789-G-A
• chr10-60278789-G-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_020987.5(ANK3):​c.399C>T​(p.Val133Val) variant causes a synonymous change. The variant allele was found at a frequency of 0.00105 in 1,613,558 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (2 hom.)
• Consequence: ANK3 NM_020987.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.18

Genes affected

ANK3 (HGNC:494): (ankyrin 3) Ankyrins are a family of proteins that are believed to link the integral membrane proteins to the underlying spectrin-actin cytoskeleton and play key roles in activities such as cell motility, activation, proliferation, contact, and the maintenance of specialized membrane domains. Multiple isoforms of ankyrin with different affinities for various target proteins are expressed in a tissue-specific, developmentally regulated manner. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain; and a carboxy-terminal regulatory domain which is the least conserved and subject to variation. Ankyrin 3 is an immunologically distinct gene product from ankyrins 1 and 2, and was originally found at the axonal initial segment and nodes of Ranvier of neurons in the central and peripheral nervous systems. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 10-60278789-G-A is Benign according to our data. Variant chr10-60278789-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 434179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000788 (120/152238) while in subpopulation AMR AF= 0.0015 (23/15284). AF 95% confidence interval is 0.00103. There are 0 homozygotes in gnomad4. There are 59 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANK3	NM_020987.5	c.399C>T	p.Val133Val	synonymous_variant	Exon 4 of 44	ENST00000280772.7	NP_066267.2
ANK3	NM_001204404.2	c.348C>T	p.Val116Val	synonymous_variant	Exon 4 of 44		NP_001191333.1
ANK3	NM_001320874.2	c.399C>T	p.Val133Val	synonymous_variant	Exon 4 of 43		NP_001307803.1
ANK3	NM_001204403.2	c.381C>T	p.Val127Val	synonymous_variant	Exon 5 of 44		NP_001191332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000280772.7	c.399C>T	p.Val133Val	synonymous_variant	Exon 4 of 44	1	NM_020987.5	ENSP00000280772.1

Frequencies

GnomAD3 genomes AF: 0.000789 AC: 120 AN: 152120 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000911

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000761 AC: 191 AN: 251078 Hom.: 1 AF XY: 0.000737 AC XY: 100 AN XY: 135678

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000810

Gnomad ASJ exome AF: 0.00457

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000926

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00107 AC: 1569 AN: 1461320 Hom.: 2 Cov.: 31 AF XY: 0.00104 AC XY: 755 AN XY: 727006

Gnomad4 AFR exome AF: 0.000299

Gnomad4 AMR exome AF: 0.000872

Gnomad4 ASJ exome AF: 0.00482

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00120

Gnomad4 OTH exome AF: 0.000977

GnomAD4 genome AF: 0.000788 AC: 120 AN: 152238 Hom.: 0 Cov.: 32 AF XY: 0.000793 AC XY: 59 AN XY: 74428

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000911

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00100 Hom.: 0

Bravo AF: 0.000922

EpiCase AF: 0.00115

EpiControl AF: 0.000830

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ANK3: BP4 -

Oct 29, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Aug 18, 2016

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	10
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs77316697; hg19: chr10-62038547;